Having morphologic features of lymphocytes and plasma cells, the lymphoplasmacytic infiltrates were strongly and diffusely positive for B-lymphocytic markers (CD20) (Fig. 2B) and plasma cells markers, including CD38 (Fig. 2C), CD138, and epithelial membrane antigen. The thickened vascular walls showed strong reactivity for kappa light chain (Fig. 2D) and no reactivity for lambda light chain (Fig. 2E). Beta-amyloid immunostaining and a Congo red special stain showed very focal, faint positivity. Liquid chromatography-mass spectrometry of the amorphous eosinophilic material identified the presence of alpha immunoglobulin heavy chains, kappa immunoglobulin light chains, and immunoglobulin J chain without evidence of amyloid deposition. The K-67 antigen proliferation index was low at 1.7%. The findings of a kappa-restricted cell population with B-lymphocytic and plasmacytic immunophenotype established the diagnosis of primary central nervous system (CNS) B-cell lymphoma with monoclonal kappa light chain deposition disease (LCDD) (aggregoma).
Cerebrospinal fluid analysis was acellular, with a negative lymphoma panel and without beta macroglobulin. Protein electrophoresis of the urine and serum was normal. Evaluation for multiple myeloma, including full-body positron emission tomography, bone scan, and bone marrow biopsy, was negative.
Postoperatively, the patient's visual acuity was 20/20 in each eye, and automated perimetry showed a left homonymous hemianopia. The remainder of the examination was normal.
Empiric treatment with low-dose radiation was initiated (total dose: 4 Gy in 2 fractions). MRI showed decrease in the right occipital lobe lesion size with a small amount of postoperative and radiation changes. Follow-up at 38 months revealed a stable ophthalmic examination and no clinical or imaging signs of active disease in the brain or elsewhere.
LCDD is characterized by clonal expansion of lymphoplasmacytic cells, overproduction of monoclonal immunoglobulin light chains, and subsequent deposition of these light chains in various tissues (1). The deposits can be parsed into amyloid and nonamyloid types. Imaging techniques cannot differentiate between the 2; their histological picture distinguishes them (2). When restricted to 1 organ, amyloid light chain deposition is far more common than nonamyloid deposition and is referred to as amyloidomas (3). Nonamyloid light chain deposition is referred to as aggregoma. Light chain deposits may be composed of either kappa or lambda light chains. In a literature review of all reported cases of LCDD, Singh et al (2) found that the deposits were derived from kappa immunoglobulin light chain in 80% of patients.
Mean age of onset of LCDD is 56 years with a 2:1 male predominance (1). The kidney is the organ most often affected, but deposits can also occur in the heart, liver, lungs, cornea, and CNS (2,4). The rarity of CNS involvement has been attributed to the selectivity of the blood–brain barrier (2).
Although most cases are associated with multiple myeloma, some are not, including our patient. There is also an association with monoclonal gammopathy of undetermined significance (1) and reports linking LCDD to other B-cell neoplasms (5). In our patient, the cellular infiltrate demonstrated the histologic and immunophenotypic features of plasma cell differentiation, adding plasma cell dyscrasias (multiple myeloma and plasmacytoma) to the differential diagnosis. However, the expression of B-lymphocyte markers such as CD20, which typically are lost during B lymphocyte to plasma cell conversion, militates against a diagnosis of plasma cell dyscrasia, and strongly favors lymphoma.
The mean survival of patients with LCDD is 4 years (6). The poor prognosis may, in part, be related to a lack of standardized treatment protocols for this rare disease. The goal of therapy is to reduce the production and deposition of immunoglobulin light chains. Low-dose radiation was the treatment modality selected for our patient, and his disease and symptoms remain stable at this time. There are reports of benefit from local resection when treating intracerebral and pulmonary deposits (2,4), but this can be difficult in patients with multifocal cerebral lesions as in our patient. Chemotherapy is another option that has been shown to offer some benefit (7,8), with melphalan and bortezomib being most frequently used. In addition, there are reports of treatment with stem cell transplantation (9).
STATEMENT OF AUTHORSHIP
Category 1: a. Conception and design: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, S. Berry, M. O. Nakawah, A. T. Whyte, G. N Fuller, and A. G. Lee; b. Acquisition of data: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, M. O. Nakawah, A. T. Whyte, and A. G. Lee; c. Analysis and interpretation of data: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, M. O. Nakawah, A. T. Whyte, and A. G. Lee. Category 2: a. Drafting the manuscript: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, M. O. Nakawah, A. T. Whyte, and A. G. Lee; b. Revising it for intellectual content: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, M. O. Nakawah, A. T. Whyte, and A. G. Lee. Category 3: a. Final approval of the completed manuscript: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, M. O. Nakawah, A. T. Whyte, and A. G. Lee.
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© 2018 by North American Neuro-Ophthalmology Society
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